Arthroscopic Treatment of Acetabular Retroversion With Acetabuloplasty and Subspine Decompression: A Matched Comparison With Patients Undergoing Arthroscopic Treatment for Focal Pincer-Type Femoroacetabular Impingement.

BackgroundGlobal acetabular retroversion is classically treated with open reverse periacetabular osteotomy. Given the low morbidity and recent success associated with the arthroscopic treatment of femoroacetabular impingement (FAI), there may also be a role for arthroscopic treatment of acetabular retroversion. However, the safety and outcomes after hip arthroscopic surgery for retroversion need further study, and the effect of impingement from the anterior inferior iliac spine (subspine) in patients with retroversion is currently unknown.HypothesisArthroscopic treatment for global acetabular retroversion will be safe, and patients will have similar outcomes compared with a matched group undergoing arthroscopic treatment for focal pincer-type FAI.Study designCohort study; Level of evidence, 2.MethodsPatients undergoing hip arthroscopic surgery for symptomatic global acetabular retroversion were prospectively enrolled and compared with a matched group of patients undergoing arthroscopic surgery for focal pincer-type FAI. Both groups underwent the same arthroscopic treatment protocol. All patients were administered patient-reported outcome (PRO) measures, including the 12-item Short-Form Health Survey (SF-12) Physical Component Summary (PCS) and a Mental Component Summary (MCS), modified Harris Hip Score (mHHS), Hip disability and Osteoarthritis Outcome Score (HOOS), and visual analog scale (VAS) for pain preoperatively and at 1 year postoperatively.ResultsThere were no differences in age, sex, or body mass index between 39 hips treated for global acetabular retroversion and 39 hips treated for focal pincer-type FAI. There were no major or minor complications in either group. Patients who underwent arthroscopic treatment for global acetabular retroversion demonstrated similar significant improvements in postoperative PRO scores (scores increased by 17 to 43 points) as patients who underwent arthroscopic treatment for focal pincer-type FAI. Patients treated for retroversion who also underwent subspine decompression had greater improvement than patients who did not undergo subspine decompression for the HOOS-Pain (33.7 ± 15.3 vs 22.5 ± 17.6, respectively; P = .046) and HOOS-Quality of Life (49.7 ± 18.8 vs 34.6 ± 22.0, respectively; P = .030) scores.ConclusionArthroscopic treatment for acetabular retroversion is safe and provides significant clinical improvement similar to arthroscopic treatment for pincer-type FAI. Patients with acetabular retroversion who also underwent arthroscopic subspine decompression demonstrated greater improvements in pain and quality of life outcomes than those who underwent arthroscopic treatment without subspine decompression

Direct Integration and Non-Perturbative Effects in Matrix Models

We show how direct integration can be used to solve the closed amplitudes of multi-cut matrix models with polynomial potentials. In the case of the cubic matrix model, we give explicit expressions for the ring of non-holomorphic modular objects that are needed to express all closed matrix model amplitudes. This allows us to integrate the holomorphic anomaly equation up to holomorphic modular terms that we fix by the gap condition up to genus four. There is an one-dimensional submanifold of the moduli space in which the spectral curve becomes the Seiberg--Witten curve and the ring reduces to the non-holomorphic modular ring of the group $\Gamma(2)$. On that submanifold, the gap conditions completely fix the holomorphic ambiguity and the model can be solved explicitly to very high genus. We use these results to make precision tests of the connection between the large order behavior of the 1/N expansion and non-perturbative effects due to instantons. Finally, we argue that a full understanding of the large genus asymptotics in the multi-cut case requires a new class of non-perturbative sectors in the matrix model.Comment: 51 pages, 8 figure

The Role of TLR4 in the Paclitaxel Effects on Neuronal Growth In Vitro

Paclitaxel (Pac) is an antitumor agent that is widely used for treatment of solid cancers. While being effective as a chemotherapeutic agent, Pac in high doses is neurotoxic, specifically targeting sensory innervations. In view of these toxic effects associated with conventional chemotherapy, decreasing the dose of Pac has been recently suggested as an alternative approach, which might limit neurotoxicity and immunosuppression. However, it remains unclear if low doses of Pac retain its neurotoxic properties or might exhibit unusual effects on neuronal cells. The goal of this study was to analyze the concentration-dependent effect of Pac on isolated and cultured DRG neuronal cells from wild-type and TLR4 knockout mice. Three different morphological parameters were analyzed: the number of neurons which developed neurites, the number of neurites per cell and the total length of neurites per cell. Our data demonstrate that low concentrations of Pac (0.1 nM and 0.5 nM) do not influence the neuronal growth in cultures in both wild type and TLR4 knockout mice. Higher concentrations of Pac (1-100 nM) had a significant effect on DRG neurons from wild type mice, affecting the number of neurons which developed neurites, number of neurites per cell, and the length of neurites. In DRG from TLR4 knockout mice high concentrations of Pac showed a similar effect on the number of neurons which developed neurites and the length of neurites. At the same time, the number of neurites per cell, indicating the process of growth cone initiation, was not affected by high concentrations of Pac. Thus, our data showed that Pac in high concentrations has a significant damaging effect on axonal growth and that this effect is partially mediated through TLR4 pathways. Low doses of Pac are devoid of neuronal toxicity and thus can be safely used in a chemomodulation mode. © 2013 Ustinova et al

Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define

The Fate of Porous Hydroxyapatite Granules Used in Facial Skeletal Augmentation

Facial appearance is largely determined by the morphology of the underlying skeleton. Hydroxyapatite is one of several materials available to enhance projection of the facial skeleton. This study evaluated the long-term maintenance of augmented bony projection when porous hydroxyapatite granules are used on the facial skeleton. Ten female patients aged 28–58 years were studied following aesthetic augmentation of the facial skeleton at 24 sites using porous hydroxyapatite granules. Postoperative CT scans at 3 months served as the baseline measurement and compared with scans taken at 1 and 2 years, with the thickness of the hydroxyapatite measured in axial and coronal planes. Thickness of original bone plus overlay of hydroxyapatite, thickness of the overlying soft tissue, and the overall projection (bone plus soft tissue) were recorded. It was found that 99.7% of the hydroxyapatite was maintained at 2 years, with no statistical difference (t test) from the baseline measurement. The overall projection (bony and soft tissue) was maintained as there was no evidence of native bone resorption or soft tissue atrophy. Radiographic results confirmed that the use of porous hydroxyapatite granules for enhancement of the facial skeleton is not only a predictable procedure, but maintains full bony projection at 2 years

Malaria is a cause of iron deficiency in African children

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334), a genetic variant that confers specific protection against malaria2, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%

Review: Current concepts in computer-assisted hip arthroscopy.

In the last 15 years, hip arthroscopy has become increasingly popular in addressing femoroacetabular impingement (FAI) because of its minimally invasive approach. However, assessing the adequacy of bone resection when correcting FAI can be difficult because visualisation and spatial awareness of the joint are poor. Recent advances in technology in the field of computer-assisted surgery and navigation and robotic surgery in orthopaedics as a resource for preoperative planning and intraoperative assistance have been widely reported. This technology is expected to upgrade surgical planning and operative techniques, decrease human error and improve patient outcomes by precisely defining the divergent anatomy and kinematics of the hip joint. This review attempts to bring the reader up-to-date with the current developments in the field of computer assisted hip arthroscopy, and discusses our experience with pre-operative planning, navigation and robotics and also provides a platform for future research in this arena

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Successful radiation treatment of anaplastic thyroid carcinoma metastatic to the right cardiac atrium and ventricle in a pacemaker-dependent patient

Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy, which is known to metastasize to the heart. We report a case of a patient with ATC with metastatic involvement of the pacemaker leads within the right atrium and right ventricle. The patient survived external beam radiation treatment to his heart, with a radiographic response to treatment. Cardiac metastases are usually reported on autopsy; to our knowledge, this is the first report of the successful treatment of cardiac metastases encasing the leads of a pacemaker, and of cardiac metastases from ATCs, with a review of the pertinent literature